Evaluation Of Endpoints Research Articles

Deep learning for oncologic treatment outcomes and endpoints evaluation from CT scans in liver cancer

Deep learning for oncologic treatment outcomes and endpoints evaluation from CT scans in liver cancer

Topographic and quantitative correlation of structure and function using deep learning in subclinical biomarkers of intermediate age-related macular degeneration.

To examine the morphological impact of deep learning (DL)-quantified biomarkers on point-wise sensitivity (PWS) using microperimetry (MP) and optical coherence tomography (OCT) in intermediate AMD (iAMD). Patients with iAMD were examined by OCT (Spectralis). DL-based algorithms quantified ellipsoid zone (EZ)-thickness, hyperreflective foci (HRF) and drusen volume. Outer nuclear layer (ONL)-thickness and subretinal drusenoid deposits (SDD) were quantified by human experts. All patients completed four MP examinations using an identical custom 45 stimuli grid on MP-3 (NIDEK) and MAIA (CenterVue). MP stimuli were co-registered with corresponding OCT using image registration algorithms. Multivariable mixed-effect models were calculated. 3.600 PWS from 20 eyes of 20 patients were analyzed. Decreased EZthickness, decreased ONLthickness, increased HRF and increased drusen volume had a significant negative effect on PWS (all p < 0.001) with significant interaction with eccentricity (p < 0.001). Mean PWS was 26.25 ± 3.43dB on MP3 and 22.63 ± 3.69dB on MAIA. Univariate analyses revealed a negative association of PWS and SDD (p < 0.001). Subclinical changes in EZintegrity, HRF and drusen volume are quantifiable structural biomarkers associated with reduced retinal function. Topographic co-registration between structure on OCT volumes and sensitivity in MP broadens the understanding of pathognomonic biomarkers with potential for evaluation of quantifiable functional endpoints.

Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL &gt; 70 or non-HDL &gt; 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI &gt; LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p &lt; 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect &lt; 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.

Abstract 4141439: Catheter ablation and clinical outcomes among older Medicare beneficiaries with atrial fibrillation

Background: Catheter ablation (CA) is increasingly used for treatment of atrial fibrillation (AF). However, CA has not been widely adopted in the older population with AF. The aim of this study is to examine the risks of adverse outcomes following CA in older people with AF. Methods: Using 2014-2019 Medicare claims, we conducted a propensity score analysis of patients treated with CA within 6 months of new AF diagnosis to patients treated with only antiarrhythmic therapy in the 6-month period. The outcome follow-up began after the 6-month period. Cox proportional hazards models were used to estimate hazard ratios (HR) for the composite and individual endpoints from CABANA trial (death, stroke, major bleeding or cardiac arrest) and CASTLE-AF trial (death or heart failure). Subgroup analyses were performed by sex, race-ethnicity, social deprivation index, frailty and dementia. Results: The study population comprised of 14623 AF patients (mean age, 76.1±7.6 years; 55% female, 28% frailty, 13% dementia), including 8% receiving CA. The mean follow-up was 1.8 years. Compared to patients with only antiarrhythmic therapy, patients treated with CA had lower rates of CABANA endpoints (CA vs antiarrhythmic therapy: 5.6 vs 11.7 per 100 person-years; HR:0.72, 95%CI:0.66-0.77) and CASTLE-AF endpoints (6.5 vs 13.8 per 100 person-years; HR:0.72, 95%CI:0.67-0.78). The benefits of CA were consistent in both female and male for CABANA endpoints (female: HR:0.71, 95%CI:0.64-0.79 and male: HR:0.72, 95%CI:0.65-0.81) and CASTLE-AF endpoints (female: HR:0.65, 95%CI:0.59-0.73 and male: HR:0.78, 95%CI:0.71-0.87), and in both frail and non-frail patients for CABANA endpoints (frail: HR:0.72, 95%CI:0.66-0.80 and non-frail: HR:0.70, 95%CI:0.63-0.77) and CASTLE-AF endpoints (frail: HR:0.89, 95%CI:0.81-0.97 and non-frail: HR:0.69, 95%CI:0.63-0.75). Similar trends were observed for subgroups defined by race-ethnicity, social deprivation index, and dementia. Conclusions: These findings suggest that CA may be beneficial for older AF patients. Nonetheless, further investigation of the safety and efficacy of CA given to older patients in well-designed interventional trials are warranted.

Abstract 4135434: Effect of early nutritional guidance for patients with acute myocardial infarction: A single center retrospective cohort study

Introduction/Background: Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis. Research Question: There remains a lack of evidence regarding the impact of early nutritionist-led dietary guidance on the prognosis of AMI patients. Aim: This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods/Approach: A retrospective cohort study enrolling 409 AMI patients who underwent emergency percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results/Data: During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance during hospitalization. The multivariate Cox regression model revealed early nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Furthermore, undernourished patients, defined as those with a geriatric nutritional risk index of 98 or less, showed a similar prognosis to those with good nutritional status after receiving nutritional guidance, indicating that nutritional guidance improves prognosis. Conclusion: Nutritionist-led dietary guidance for patients with AMI can potentially improve total mortality and is expected to be more effective in undernourished patients. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Abstract 4120785: Differential Cardiovascular Impact of ω-3 Fatty Acid in Patients at High Cardiovascular Risk in Asians versus non-Asians: Sub-analysis of the STRENGTH Randomized Clinical Trial

Background: Racial differences in lipid and cardiovascular risk profiles are well-established including for Asians. The STRENGTH trial found that ω-3 carboxylic acid (CA) formulation of eicosapentaenoic acid and docosahexaenoic acid did not result in significant changes in cardiovascular event rates compared with corn oil in statin-treated patients at high cardiovascular risk, however drug efficacy may vary by race. We evaluated and compared the cardiovascular treatment effect of ω-3 CA between Asians and non-Asians in this sub-analysis of the STRENGTH trial. Methods: The STRENGTH trial was a double-blinded 1:1 randomized controlled trial of 13,078 high cardiovascular risk patients enrolled during 10/30/2014-6/14/2017 at 675 centers. Efficacy of ω-3 CA for Asians (n=1,355) and non-Asians (n=11,723) and interactions between race and treatment effect were assessed. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial infarction, stroke, coronary revascularization and unstable angina hospitalizations. Results: Key differences in baseline characteristics include Asians having significantly higher prevalence of men, secondary prevention, and lower total cholesterol, LDL, apoB100, and hsCRP. In Asians, ω-3 CA was associated with significantly lower primary endpoint during follow-up, with 81/698 events [Kaplan-Meier (KM) Estimate: 14.8%] in the ω-3 CA group, 103/657 events (KM Estimate: 20.4%) in the corn oil group, and hazard ratio (HR) 0.72, 95% CI 0.54-0.96, P=0.026 (Figure A). In non-Asians, there was not a significant difference in primary endpoint rates between the two groups, with 704/5841 events (KM Estimate: 15.6%) in the ω-3 CA group, 692/5882 events (KM Estimate: 15.9%) in the corn oil group, and HR 1.03 95% CI 0.93-1.14, P=0.60 (Figure B). There were significant interactions between race (Asian versus non-Asian) and treatment group for the primary endpoint (P=0.021) and non-fatal stroke (P=0.016) and remained significant after adjusting for other covariates. Conclusion: ω-3 CA was associated with significant reduction in major adverse cardiovascular events compared with corn oil in Asians but not in non-Asian patients with high cardiovascular risk. Further research is necessary to elucidate the mechanisms for potentially beneficial effects of ω-3 CA unique to Asian race.

Abstract 4138704: Safety and Efficacy of Generic Atorvastatin in Korean Dyslipidemia Patients: A Non-Interventional Observational Study

Background: Statins are widely used for controlling dyslipidemia. However, most evidences for dyslipidemia prevention and treatment with statins are based on studies involving Caucasian populations, resulting in limited data on Korean patients. This study was conducted to evaluate the efficacy lipid profile and safety of generic atorvastatin in a real-world clinical setting among Korean dyslipidemia patients. Methods: This study was conducted as a non-interventional, multi-center observational study. It was carried out across 264 institutions and clinics from October 2017 to July 2021. Total 16,992 participants were enrolled. The safety and efficacy evaluation cohorts consisted of 16,803 and 11,035 subjects, respectively. The liver function evaluation cohort included 13,889 subjects. The main eligibility criteria were dyslipidemia patients prescribed generic atorvastatin according to approved indications. Adverse event rates were collected for safety evaluation, and lipid profiles, including LDL-C, were collected for efficacy evaluation. Results: In the safety endpoint evaluation, 1,612 adverse events were reported in 1,027 subjects (6.11%). Common adverse events such as dizziness, headache, and constipation, which were frequently observed in this study, were within the approved labels. Muscle pain occurred in 0.14% of subjects, and myopathy, myositis, rhabdomyolysis, and CK abnormalities or increases were reported in 0.01% of subjects, respectively. Most of the adverse events were confirmed to be mild or resolved, and the study was completed without changing the dose. All abnormal liver function test results were reported in less than 1% of subjects (AST increase: 0.14%, ALT increase: 0.1%, ALP increase: 0.01%, γ-GT increase: 0.01%). The mean LDL-C decreased from 117.31 mg/dL to 89.97 mg/dL, showing a statistically significant improvement in LDL-C levels (p &lt; 0.0001). Conclusions: Generic atorvastatin demonstrated tolerable safety as well as significant efficacy on lipid profile. Generic atorvastatin might be safe and effective for Korean patients with dyslipidemia.

INNV-33. ADVANCING PRECISION TREATMENT FOR DIFFUSE MIDLINE GLIOMA: THE DMG LEARNING HUB INITIATIVE

Abstract Diffuse Midline Glioma (DMG) poses a significant challenge in neuro-oncology due to its heterogeneous presentation and limited therapeutic options. Clinical trials often serve as the primary avenue for treatment, yet families encounter numerous barriers in navigating and selecting appropriate trials. Health disparities, including disparities in medical literacy and access to specialized medical centers, further complicate decision-making processes. Existing registries lack comprehensive data integration, focusing on isolated perspectives of either research or clinical data, neglecting the holistic patient profile. Evaluation of treatment endpoints beyond Progression-Free Survival (PFS) and Overall Survival (OS) remain inconsistent, despite being a priority for families. The DMG Learning Hub emerges as a transformative platform designed to empower families by offering informed options and guidance while fostering a collaborative environment where patient families actively contribute to shaping the landscape of clinical trials. Leveraging AI-assisted matching, the platform assists families in navigating the complex decision-making process surrounding clinical trial participation. The inclusion of a patient-reported outcome journal feature enables families to track vital information such as symptom changes and supplement usage, with autonomy over the timing of shared data. Using real-time data sharing facilitates invaluable insights for researchers, bridging gaps that would otherwise be overlooked and enriching the collective understanding of DMG. Harmonizing molecular, imaging, and clinical data within the platform equips care teams with comprehensive, near-real-time information crucial for personalized treatment strategies. This integrated approach not only supports the inclusion of n-of-1 arms in current trials but also extends therapeutic opportunities to patients previously ineligible for studies due to specific disease markers or progression patterns. The DMG Learning Hub represents a significant stride towards precision oncology by synergizing patient-centric priorities with cutting-edge technology, integrating harmonized data, and fostering collaborative efforts, the initiative heralds a promising era of personalized treatment for DMG and beyond the neuro-oncology community.

Persistently low tricuspid annular plane systolic excursion and its prognosis in Japanese hospitalized patients with heart failure with reduced ejection fraction.

In patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF), low tricuspid annular plane systolic excursion (TAPSE) on echocardiography is associated with poor prognosis. The significance of TAPSE changes post-HF treatment among HFrEF patients remains unclear. We evaluated the factors associated with persistently low TAPSE and its prognostic impact in Japanese hospitalized patients with HFrEF. We prospectively examined 260 HFrEF patients from the prospective observational HIJ-HF III study of HF patients hospitalized at Tokyo Women's Medical University between 2015 and 2019. Persistently low TAPSE was defined as TAPSE < 17mm on both pre- and 1-year post-discharge echocardiography. The primary endpoint of the study was all-cause mortality or re-hospitalization due to HF. Prognosis and characteristics were compared between patients with and without persistently low TAPSE. Using characteristics and echocardiography data, factors associated with persistently low TAPSE were assessed using logistic regression analysis. We identified the prognostic impact of persistently low TAPSE in HFrEF patients using Cox proportional hazards models. Seventy-eight (30%) of the 260 patients had persistently low TAPSE. They had higher New York Heart Association functional class; lower baseline TAPSE and left ventricular ejection fraction; and fewer angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Significant factors associated with persistently low TAPSE included higher brain natriuretic peptide level at 1year after discharge, lower baseline levels of TAPSE and septal s'. Over a follow-up period of 32months (range 12-69months) after the 1-year echocardiography, the rate of the primary endpoint was significantly higher among patients with persistently low TAPSE than that among others (n = 31 (40%) vs. n = 39 (21%), respectively, log-rank p < 0.001). Cox multivariate analysis revealed that persistently low TAPSE was independently associated with adverse events (Hazard ratio, 1.975; 95% confidence interval 1.183-3.295; p = 0.009). Exactly 30% of hospitalized patients with HFrEF had low TAPSE both pre- and 1-year post-discharge. Persistently low TAPSE had independent predictive value of prognosis in these patients.

Pooled safety analysis from the VOLTAIRE clinical trials of adalimumab-adbm and adalimumab reference product in patients with rheumatoid arthritis, Crohn’s disease, and chronic plaque psoriasis

ABSTRACT Objectives This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn’s disease (CD), and chronic plaque psoriasis (PsO) who received ≥ 1 dose of adalimumab-adbm or adalimumab reference product (RP). Methods Exposure-adjusted incidence rates for safety endpoints were calculated per 100 patient-years and reported by disease indication and treatment arm. Subgroup analyses by patient age and sex were also conducted. Results The mean length of follow-up was 62 weeks, 48 weeks, and 32 weeks for patients with RA, CD, and PsO, respectively. Rates of SAEs and discontinuations due to AEs were similar among patients with RA and PsO, but slightly higher among those with CD. Incidence rates of all safety endpoints were consistent between the adalimumab-adbm and adalimumab RP treatment arms within each indication Subgroup analyses of patients with RA, CD, and PsO showed no between-group differences by age and sex. Conclusions In patients with RA, CD, and PsO, there were no differences between biosimilar adalimumab-adbm or the adalimumab RP regarding the rate of adverse events, serious adverse events, discontinuations due to adverse events, deaths, or any adverse events of special interest.

Predictors and Outcomes of Inappropriate Dosing of Direct Oral Anticoagulants in Patients Receiving Transcatheter Aortic Valve Implantation.

Direct oral anticoagulant (DOAC) dose adjustment is based on age, renal function, and body weight. There is a paucity of data describing the factors associated with the prescription of inappropriate dosage and their impact on clinical outcomes among patients receiving transcatheter aortic valve implantation (TAVI). In a single-center study, 432 patients who were on long-term DOAC therapy and underwent TAVI between 2015 and 2022 were included. We analyzed the predictors and outcomes of inappropriate dosing of DOACs; namely apixaban, dabigatran, edoxaban, and rivaroxaban. A composite endpoint, including all-cause mortality, life-threatening/major bleeding, stroke, peripheral thromboembolic complications, or myocardial infarction, was assessed after 1 year. In this TAVI cohort, inappropriate DOAC dosing was observed in 20.6% of patients. Inappropriate DOAC dosage was related to female gender (adj. odds ratio [OR] 2.72, 95% confidence interval [CI] 1.64-4.51, p < 0.001) as well as lower estimated glomerular filtration rate (eGFR) (adj. OR 0.99, 95% CI 0.98-1.00, p = 0.019), and to the administration of non-rivaroxaban DOACs (adj. OR 0.28, 95% CI 0.16-0.50, p < 0.001). After 1 year, patients on both appropriate and inappropriate DOAC dosage exhibited comparable rates of the composite endpoint (OR 0.88, 95% CI 0.53-1.46, p = 0.622). Old age (adj. OR 1.05, 95% CI 1.01-1.10, p = 0.018) as well as anemia (adj. OR 0.86, 95% CI 0.75-0.99, p = 0.031) emerged as independent predictors of the composite endpoint. In this TAVI cohort, female gender and renal insufficiency were associated with inappropriate DOAC dosage, whereas rivaroxaban was linked to appropriate dosing. Inadequate DOAC dosage did not translate into a worse outcome in our TAVI population. Prospective Segeberg TAVI Registry (ClinicalTrials.gov identifier: NCT03192774).

Impact of Optimal Procedural Result After Transcatheter Edge-to-Edge Tricuspid Valve Repair: Results From TRI-SPA Registry.

Procedural success following tricuspid transcatheter edge-to-edge repair (TEER) has been defined variably over time; however, the consequences of achieving a tricuspid regurgitation (TR) grade of 0/1+ are still unclear. This study aimed to assess the predictors and prognostic impact of achieving TR 0/1+ after TEER and its role in clinical events. This multicenter registry included patients undergoing tricuspid TEER in 15 Spanish centers from June 2020 and May 2023. Patients were categorized into the following groups based on the TR grade after procedure: optimal (0/1+), acceptable (2+), and not acceptable (≥3+). The primary endpoint was the 1-year composite of all-cause death, heart failure hospitalization, and tricuspid reintervention. Secondary endpoints included each component of the primary endpoint assessed separately, NYHA functional class, and TR grade at follow-up. Among 280 enrolled patients, 120 (42.9%) had residual TR 0/1+, 111 (39.6%) had residual TR 2+, and 49 (17.5%) had residual TR≥3+. Patients with TR 0/1+ experienced lower rates of the primary endpoint (13% vs 20% vs 31%; log-rank P=0.036). Residual TR≥3+ was an independent predictor of primary endpoint (HR: 2.277; P = 0.044). Higher rates of NYHA functional class I or II and sustained TR reduction were seen in the TR 0/1+ group (P< 0.001 for both). A small coaptation gap and absence of septal leaflet tethering were independent predictors of achieving TR 0/1+. An optimal procedural result after TEER might be associated with improved outcomes. TR coaptation gap and leaflet restriction may aid in assessing suitability for TEER.

Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial

Tenecteplase has potential benefits over alteplase, the standard agent for intravenous thrombolysis in acute ischaemic stroke, because it is administered as a single bolus and might have superior efficacy. The ATTEST-2 trial investigated whether tenecteplase was non-inferior or superior to alteplase within 4·5 h of onset. We undertook a prospective, randomised, parallel-group, open-label trial with masked endpoint evaluation in 39 UK stroke centres. Previously independent adults with acute ischaemic stroke, eligible for intravenous thrombolysis less than 4·5 h from last known well, were randomly assigned 1:1 to receive intravenous alteplase 0·9 mg/kg or tenecteplase 0·25 mg/kg, by use of a telephone-based interactive voice response system. The primary endpoint was the distribution of the day 90 modified Rankin Scale (mRS) score and was analysed using ordinal logistic regression in the modified intention-to-treat population. We tested the primary outcome for non-inferiority (odds ratio for tenecteplase vs alteplase non-inferiority limit of 0·75), and for superiority if non-inferiority was confirmed. Safety outcomes were mortality, symptomatic intracranial haemorrhage, radiological intracranial haemorrhage, and major extracranial bleeding. The trial was prospectively registered on ClinicalTrials.gov (NCT02814409). Between Jan 25, 2017, and May 30, 2023, 1858 patients were randomly assigned to a treatment group, of whom 1777 received thrombolytic treatment and were included in the modified intention-to-treat population (n=885 allocated tenecteplase and n=892 allocated alteplase). The mean age of participants was 70·4 (SD 12·9) years and median National Institutes of Health Stroke Scale was 7 (IQR 5-13) at baseline. Tenecteplase was non-inferior to alteplase for mRS score distribution at 90 days, but was not superior (odds ratio 1·07; 95% CI 0·90-1·27; p value for non-inferiority<0·0001; p=0·43 for superiority). 68 (8%) patients in the tenecteplase group compared with 75 (8%) patients in the alteplase group died, symptomatic intracerebral haemorrhage (defined by SITS-MOST criteria) occurred in 20 (2%) versus 15 (2%) patients, parenchymal haematoma type 2 occurred in 37 (4%) versus 26 (3%) patients, post-treatment intracranial bleed occurred in 94 (11%) versus 78 (9%) patients, significant extracranial haemorrhage occurred in 13 (1%) versus six (1%) patients, respectively, and angioedema occurred in six (1%) participants in both groups. Tenecteplase 0·25 mg/kg was non-inferior to 0·9 mg/kg alteplase within 4·5 h of symptom onset in acute ischaemic stroke. Easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischaemic stroke. The ATTEST-2 population was large and representative of thrombolysis-eligible patients in the UK and, together with findings from other trials, provides robust evidence supporting the introduction of tenecteplase in preference to alteplase. The Stroke Association and British Heart Foundation.

Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification

Abstract Background The clinical chemistry score (CCS) comprising high-sensitivity (hs) cardiac troponins (cTn), glucose and estimated glomerular filtration rate has been previously validated with superior accuracy for detection and risk stratification of acute myocardial infarction (AMI) compared to hs-cTn alone. Methods The CCS was directly compared to other biomarker-based algorithms for rapid rule-out and prognostication of AMI including the hs-cTnT limit-of-blank (LOB, &amp;lt;3 ng/L) or limit-of-detection (LOD, &amp;lt;5 ng/L) and the dual marker strategy (DMS) (copeptin &amp;lt;10 pmol/L and hs-cTnT ≤14 ng/L) in 1506 patients presenting to the emergency department (ED) with symptoms suggestive of acute coronary syndrome. Negative predictive values (NPV) and sensitivities for rule-out of AMI were assessed and outcomes included rates of the combined end-point of all-cause mortality, myocardial re-infarction and stroke within 12 months. Results NPVs of 100% (98.3-100%) could be found for a CCS=0, hs-cTnT LoB and hs-cTnT LoD with rule-out efficacies of 11.1%, 7.6% and 18.3% as well as specificities of 13.0% (9.9-16.6%), 8.8% (7.3-10.5%) and 21.4% (19.2-23.8%), respectively. A CCS≤ 1 achieved a rule-out in 32.2% of all patients with a NPV of 99.6% (98.4-99.9%) and specificity of 37.4% (34.2-40.5%) compared to a rule-out efficacy of 51.2%, NPV of 99.0 (98.0-99.5) and specificity of 59.7% (57.0-62.4%) for the DMS. Rates of the combined end-point of death/AMI within 30 days ranged between 0.0% and 0.5% for all fast-rule-out protocols. Conclusions The CCS enables a reliable rule-out of AMI with low outcome rates in short and long-term follow-up for a specific population of ED patients. However, compared to a single or dual biomarker strategy, the CCS rule-out is attenuated by a loss of specificity and lower efficacy. Thus, the clinical benefit of the CCS in clinical practice seems to be negligible.

Effect of nutritional guidance on mortality and composite endpoints in patients with acute myocardial infarction: a single center retrospective cohort study

Abstract Background/Introduction Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis (1,2). While reports suggest the efficacy of the Mediterranean diet, there remains a lack of evidence regarding the impact of nutritionist-led dietary guidance on the prognosis of AMI patients. Purpose This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods A retrospective cohort study was conducted, enrolling 446 consecutive AMI patients who underwent emergency coronary angiography and percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Patients meeting the universal definition of myocardial infarction were included (3). After excluding 37 in-hospital deaths, evaluations for all-cause mortality, cardiovascular mortality, and composite endpoints were performed during follow-up in 409 patients. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Additionally, 15 cases of nonfatal stroke (3.7%), 17 cases of nonfatal acute coronary syndrome (4.2%), and 20 cases of hospitalizations for acute decompensated heart failure (4.9%) were observed. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance. The multivariate Cox regression model incorporated all variables exhibiting statistically significant associations with long-term mortality, and the primary composite endpoints. The multivariate Cox regression model revealed nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Conclusion Nutritional guidance for AMI patients may improve overall mortality. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Fractional flow reserve versus solely angiography-guided revascularisation in coronary artery disease, systematic review and meta-analysis

Abstract Objective Subsequent randomised controlled trials (RCTs) comparing the clinical outcomes of fractional flow reserve (FFR)-guided and angiography-guided revascularisation in patients with coronary artery disease (CAD) yielded inconsistent results. Moreover, recent European Society of Cardiology (ESC) guidelines lowered recommendation for FFR use in acute coronary syndorme (ACS). This study aimed to assess head to head whether FFR-guided revascularisation reduces the rates of hard clinical endpoints in comparison with the angiography-guided approach alone. Methods A systematic review was conducted through October 2023 at Embase, Clinicaltrials.gov, Cochrane Library, and EBSCO. Only RCTs that evaluated stable and unstable CAD and acute myocardial infarction (MI) were included. The trials selection was performed according to the latest ESC guidelines. Meta-regression analysis was performed to assess the impact of observation time on outcomes. Results Overall, 11 571 records were screened for relevant studies. Eight RCTs involving 4713 patients were included in the meta-analysis. FFR guidance was associated with a significant reduction of MI (RR, 0.75 [95% confidence interval {Cl}, 0.58–0.96], p=0.02) and lower rate of revascularisation (standardised mean difference - 0.12, [95% Cl, -0.14–-- 0.09], p&amp;lt;00001). There were no differences between FFR-guided and angio-guided revascularisation in MACE (RR, 0.84 [95% Cl, 0.69–1.02], p=0.08), all-cause mortality (RR, 1.00 [95% Cl, 0.58–1.74], p=0.99), and unplanned revascularisation (RR, 0.89 [95% Cl, 0.72–1.10], p=0.28). The meta-regression analysis revealed a significant impact of the duration of follow-up for MACE, all-cause mortality and MI, but not for unplanned revascularisation. Conclusions FFR-driven revascularisation was associated with a significantly lower rate of MI for entire population and also in the ACS subset. These results were achieved with a substantially less revascularisations compared with solely angiographic guidance.

Efficacy and safety of long-term edoxaban treatment for low body weight cancer patients with isolated distal deep vein thrombosis: a post-hoc subgroup analysis of the ONCO DVT study

Abstract Background Low body weight is known to be a bleeding risk in the anticoagulation treatment. ONCO DVT study revealed that 12-month edoxaban treatment for cancer patients with isolated distal deep vein thrombosis (DVT) reduced a composite outcome of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death compared with 3-month edoxaban treatment. However, the efficacy and safety of long-term edoxaban treatment for cancer patients with low body weight is unclear. Purpose In this subgroup analysis, we assessed the efficacy and safety of 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT. Methods We conducted a post-hoc subgroup analysis of the ONCO DVT study in the low body weight patients. ONCO DVT study was a multicenter, open-label, adjudicator-blinded, randomized clinical trial. Cancer patients with isolated distal DVT were assigned to 12-month or 3-month edoxaban treatment. The primary endpoint was a composite outcome of a symptomatic recurrent VTE or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months. We enrolled patients who met low body weight defined in Japanese Version of High Bleeding Risk criteria (&amp;lt;55 kg for men, &amp;lt;50 kg for women) and evaluated the efficacy and safety of 12-month edoxaban treatment using logistic regression models and log-rank test. Results Among 601 patients in the intention-to-treat population of ONCO DVT study, 322 patients (53.6%) met low body weight: 151 patients were in 12-month edoxaban group and 171 patients were in 3-month edoxaban group. The body weight was similar between two group (47.1±5.2 kg in 12-month edoxaban group vs. 46.9±5.4 kg in 3-month edoxaban group; P=0.77). All of them used a lower dose edoxaban (30 mg once daily) following the dose reduction criteria. 12-month edoxaban group had lower rates of the primary endpoint compared with 3-month edoxaban group (2 patients (1.3%) vs. 10 patients (5.8%); Odds ratio 0.22 [95% CI, 0.05–1.00]; Log-rank P=0.036). There was no significant difference in the major secondary endpoint of major bleeding (12 patients (7.9%) in 12-month edoxaban group vs. 16 patients (9.4%) in 3-month edoxaban group; Odds ratio 0.83 [95% CI, 0.38–1.83]; Log-rank P=0.65). All clinically relevant bleeding events occurred in 22 patients (14.6%) in 12-month edoxaban group and in 27 patients (15.8%) in 3-month edoxaban group (Odds ratio 1.40 [0.90–2.19]; Log rank P=0.13), resulting in the comparable risk of bleeding in the 12-month edoxaban group. Conclusions Our study suggests that 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT prevents recurrent VTE or VTE-related death without increasing the risk of bleeding compared to 3-month edoxaban treatment.primary endpointsecondary endpoint

Clinical outcomes according to residual cholesterol and inflammatory risk in patients undergoing PCI

Abstract Background Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) and low grade vascular inflammation, commonly quantified using high-sensitivity C-reactive protein (hsCRP), have been demonstrated to be causal in the development of atherosclerotic disease. Whilst recent large-scale trials have investigated the relative impact of LDL-c and inflammation on cardiovascular outcomes, there is a scarcity of data in real-world patients undergoing percutaneous coronary intervention (PCI). Purpose To investigate the relative drivers of residual risk in patients with established statin treatment undergoing PCI in a contemporary large-scale cohort. Methods From January 2012 to February 2020 patients undergoing PCI at a tertiary center were included for current analysis. Patients were categorized into 4 subgroups according to different combinations of LDL-c and hsCRP concentrations at baseline: no residual cholesterol or inflammatory risk (LDL-c &amp;lt;70 mg/dL + hsCRP &amp;lt;2 mg/L), residual cholesterol risk (LDL-c ≥70 mg/dL + hsCRP &amp;lt;2 mg/L), residual inflammatory risk (LDL-c &amp;lt;70 mg/dL + hsCRP ≥2 mg/L), and combined residual cholesterol and inflammatory risk (LDL-c ≥70 mg/dL + hsCRP ≥2 mg/L). Individuals who presented with acute myocardial infarction, neoplastic disease and hsCRP concentrations &amp;gt;10 mg/l were excluded. The outcome of interest was major adverse cardiac events (MACE - composite of all-cause mortality, myocardial infarction, or stroke). A univariable cox regression model was calculated. Results Overall, 10,845 patients were included. In total, 3,210 patients displayed neither cholesterol nor inflammatory risk and 3,059 individuals had elevated cholesterol risk only. In 1,839 patients an inflammatory risk was noted, whilst 2,737 patients presented with combined cholesterol and inflammatory risk. Kaplan-Meier curves for 1-year follow-up are displayed in Figure 1. Patients with residual inflammatory risk had the highest event rate of the composite endpoint (5.2%), followed by patients with combined residual risk (3.5%), individuals with residual cholesterol risk (2.3%) and persons with neither cholesterol nor inflammatory risk (2.4%; p&amp;lt;0.0001 for log rank test across all groups). An association with MACE was solely documented for patients with residual inflammatory risk (HR: 2.09, 95% CI: 1.52 - 2.88; p&amp;lt;.001), and also borderline significant for combined cholesterol and inflammatory risk (HR: 1.41, 95% CI: 1.03 - 1.95; p=0.034), whilst this was not the case for patients with elevated cholesterol risk only (see Figure 2). Conclusion In a contemporary real-world cohort of statin treated patients undergoing PCI, inflammation irrespective of LDL-c concentrations was the driver for adverse cardiovascular outcomes. This data might be helpful to further define target populations for both intensified lipid-lowering as well as anti-inflammatory treatment approaches.

Real-world implementation of a genotype-guided p2y12-inhibitor de-escalation strategy in acute coronary syndrome patients

Abstract Background CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel, may optimize the balance between ischemic and bleeding risk in ACS patients. Purpose Compare bleeding and ischemic event rates in genotyped patients versus standard care. Methods Since 2015, ACS patients in the FORCE-ACS registry received standard dual antiplatelet therapy (DAPT). Since 2021, immediate genotype-guided P2Y12-inhibitor de-escalation was applied, switching non-carriers of the loss-of-function allele CYP2C19*3 or CYP2C19*2 from ticagrelor or prasugrel to clopidogrel, while loss-of-function carriers, carrying at least one loss-of-function allele, remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction (MI) or stroke and the primary bleeding endpoint, BARC 2, 3, or 5 bleeding, were compared between genotyped those on standard DAPT after one year. Results Among 5,321 enrolled ACS patients, 406 underwent genotyping, compared with 4,915 non-genotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were non-carriers, whereas 34.7% (n=141) were loss-of-function carriers. The primary ischemic endpoint occurred in 5.2% of patients in the genotyped cohort compared to 6.9% in the standard care cohort (adjHR 0.88, 95% CI 0.56–1.38). The rate of the primary bleeding endpoint was lower in the genotyped cohort compared to the standard care cohort (4.7% vs. 9.8%; adjHR 0.50, 95% CI 0.31-0.78). Conclusion These results demonstrate the feasibility of a CYP2C19 genotype-guided P2Y12-inhibitor de-escalation strategy in a real-world ACS population. This strategy reduced bleeding events, while ischemic events were not increased as compared to a standard DAPT regime.Primary ischemic endpointBARC 2, 3 or 5 bleeding

Association between completeness of revascularization and cardiovascular outcomes in patients with diabetes and non-ST elevation myocardial infarction: a population-based registry analysis

Abstract Introduction Approximately one-third of the patients presenting with non-ST elevation myocardial infarction (NSTEMI) have diabetes. From these, two-thirds have multivessel coronary disease. The impact of completeness of revascularization in this population remains unclear. Purpose To evaluate the contemporary patterns of coronary revascularization among patients with diabetes and NSTEMI, and the clinical outcomes stratified by anatomic completeness of revascularization. Methods All patients with diabetes and multivessel disease admitted for NSTEMI between April 2009 and March 2020 in Ontario, Canada were included. Patients with previous coronary artery bypass graft surgery (CABG) at any time, percutaneous coronary intervention (PCI) in the previous 90 days, or shock were excluded. Patients were classified in four groups, from the most to the least complete revascularization strategy: CABG, complete revascularization with PCI, incomplete revascularization with PCI, or no revascularization. Outcomes included all-cause death and the composite of all-cause death, myocardial infarction, and stroke. Multivariable Cox regression was used to account for confounding (demographics, comorbidities, left ventricular function, coronary anatomy, laboratory tests, and diabetes treatment). Results We included 14,511 patients (mean age: 68.7±11.5y; 69.6% males). A total of 4,525 (31.2%) patients were treated with CABG, 3,008 (20.7%) with complete PCI, 3,624 (25.0%) with incomplete PCI and 3,354 (23.1%) were not revascularized. Patients with more complex coronary disease were more frequently treated with CABG, while PCI was more common in those with less complex disease (p&amp;lt;0.001; Fig 1). The mean number of grafts in the CABG group was 3.4±1.0. The mean number of stents in the complete and incomplete PCI groups was 2.4±1.3 and 1.7±0.9, respectively. Adjusted 5-y risks of all-cause death following CABG, complete PCI, incomplete PCI and no revascularization were, respectively, 25.9%, 29.8%, 32.2%, and 39.4%. Over a median follow-up of 5.8ys, CABG was associated with reduced all-cause death compared with complete PCI (HR 0.82; 95%CI 0.75 - 0.90), incomplete PCI (HR 0.73; 95%CI 0.67 - 0.80), or no revascularization (HR 0.54; 95%CI 0.50 - 0.58); p&amp;lt;0.001 for all (Fig 2). Adjusted 5-y risks of the composite endpoint following CABG, complete PCI, incomplete PCI and no revascularization were, respectively, 34.0%, 41.5%, 44.6%, and 52.9%. CABG was associated with reduced rates of the composite endpoint compared with complete PCI (HR 0.75; 95%CI 0.69 - 0.81), incomplete PCI (HR 0.67; 95%CI 0.62 - 0.72), or no revascularization (HR 0.50; 95%CI 0.47 - 0.54); p&amp;lt;0.001 for all. Conclusion In this contemporary real-world cohort study, almost a quarter of the patients with diabetes and NSTEMI did not receive any revascularization procedure. Cardiovascular outcomes were incrementally improved with CABG or complete revascularization with PCI, compared to no revascularization.Figure 1Figure 2